Methods and compositions for relief of gas-caused gastrointestinal distress in warm-blooded animals



United States Patent METHODS AND COMPOSITIONS FOR RELIEF OF GAS-CAUSED GASTROINTESTIN AL DISTRESS IN WARM-BLOODED ANIMALS Bruno Puetzer, White Plains, Leonard Mackles, New York, and Martin M. Perl, Brooklyn, N.Y., assignors, by mesne assignments, to Tintex Corporation, Revlon, Inc., New York, N.Y., a corporation of Delaware No Drawing. Filed Nov. 14, 1963, Ser. No. 323,554

11 Claims. (Cl. 167-55) This invention relates, in general, to the treatment of certain transient disorders of the gastrointestinal system and to novel compositions of matter and therapeutic techniques suitable for treatment of the same. In particular, the invention is concerned with the treatment of transient distresses of the gastrointestinal system caused by, or attributable to, the accumulation and/ or adherence of gas in and to the gastrointestinal tract, and incorporates, in its broadest aspects, the provision of unique therapeutic compositions designed to provide relief from symptoms accompanying these types of distresses.

The accumulation and adherence of gas within the gastrointestinal system is usually evidenced, in general, by such symptoms as excessive belching, distension, borborygmus and flatulence. The foregoing symptoms are quite common, and usually result from the ingestion of excessive air resulting from normal digestive tendencies, but, more usually, asa result of excessive drinking, smoking or eating, or as a result of gases produced by fermentative processes or by hyperactivity of the bowel and rapid emptying of the stomach, among other actions or reactions of the digestive process. The apparent inability of the gastrointestinal system to eliminate excessive quantities of such gas usually results in the entrapment and accumulation of the same as numerous bubbles or air pockets within the gastric and intestinal fluids. For the most part, these bubbles or air pockets are encased within a relatively viscous mucus which accounts, in part, for their stability, and, so to speak, adherence within the digestive system, as well as for the attendant difiiculties in providing effective means for their elimination. Moreover, it has been demonstrated that such gaseous bubbles or air pockets exhibit a tendency to adhere to the gastrointestinal tract in much the same manner as equivalent gaseous occurrences within confined liquid systems, resulting in the physical characteristic generally referred to as foaming. This characteristic foaming not only results in irritation and distension of the gastrointestinal tract, per se, but in addition, renders difiicult the treatment of the primary causative factors which produce the same.

Heretofore, numerous proposals have been advanced towards providing relief from the distressing symptoms caused by such gas accumulation, but, in general, these have been restricted to the administration, via the oral route, of one or more types of naturally-occurring or synthetically-produced compositions serving to reduce the capacity of the gastric and intestinal fluids to entrap the gases in the first instance, or towards providing effective relief whereby the stability of the gas bubbles or gas pockets is materially reduced. By way of summary, it may be said that such prior approaches differ to the extent that one type of composition is intended to provide an antifoaming effect (i.e., preventive) whereas others are intended to provide direct defoaming activity (i.e., curvative).

More recently, one of the most acceptable methods for providing relief from distress caused by the accumulation and adherence of gas in and to the walls of the intestinal tract involves the administration of silicone-antifoaming agents to the afiiicted host, and, whereas, this technique was initially employed with complete success in the treat- Patented Nov. 28, 1967 ment of bloat in ruminants, it has not, insofar as we have been able to ascertain, been applied with complete success for the treatment of analogous distresses within human beings. In point of fact, whereas such treatments have been found to be moderately beneficial and useful towards alleviating distresses due to gas accumulation and the like within the human fastrointestinal system, they have not proved to be entirely satisfactory for a number of reasons which shall become more obvious from the discussions and accumulated data presented hereinafter.

The present invention is based, in part, on our discovery that the combination of a metal salt of a fatty acid, mineral oil, microcrystalline wax and a suitable dispersing agent such as a fatty acid ester of a polyhydric alcohol constitutes a unique composition which is remarkably effective in reducing the tendency of gases to become entrapped in gastric and intestinal fluids, particularly those containing a high amount of mucus, and which is, in addition, highly effective in providing a rapid release of entrapped air therefrom. Our discovery, in efifect, makes possible the provision of novel therapeutic compositions and methods ideally suitable for obtaining relief from the distressing symptoms caused by the accumulation and adherence of gas in and to the Walls of the gastrointestinal tract.

In accordance with the present invention, the combination of a salt of a fatty acid, mineral oil, microcrystalline Wax and a suitable dispersing agent such as a fatty acid ester of a polyhydric alcohol which comprise our novel therapeutic compositions can be selected from a wide variety of appropriate materials within their respective classes so long as they are non-toxic and physiologically inert to the digestive process. As far as can be determined all materials falling within the classes specified hereinafter meet these limitations.

Thus, the metal salts of fatty acids employed as one essential ingredient of our novel compositions include the conventional fatty acid salts of the mono-, di-, and trivalent metals, as for example the fatty acid salts of the alkali, alkaline earth and other metals such as sodium, potassium, calcium, zinc, magnesium, aluminum and the like. The fatty acids employed to react with such metals to produce salts useful in the practice of our invention are those saturated and unsaturated organic acids which contain from approximately 6 to 22 carbon atoms. For the most part, such acids are mono'basic in character and include, as for example, oleic, linoleic, linolenic, palmitic, stearic and the like materials. With but few exceptions, the metal salts of fatty acids are generally referred to as metal soaps and those soaps which We prefer to employ in our therapeutic compositions are the divalent'metal soaps such as magnesium stearate, calcium stearate, zinc stearate and the corresponding oleates and palmitates. The aluminum soaps also represent an effective type of metal soap useful in the practice of our invention.

In physical form, metal soaps are usually light powders, and are in most instances tasteless, odorless and insoluble in Water. The amount of metal soap we employ may vary over a wide range. For example, we have used as little as S and as much as 20 percent by weight of this ingredient within our compositions with entirely satisfactory results. Preferably, however, we employ the metal soap in amounts which vary from about 8 to 16 percent by weight of the composition. Particularly good results have been obtained when the metal soap is employed in an amount of about 13 percent by weight of the therapeutic composition.

As the mineral oil ingredient of our novel compositions, we can employ any of the liquid products of petroleum within the viscosity range of products generally referred to as white oils. These materials are nonreactive, non irritating and completely innocuous, as well as bacteriostatic and fungistatic. We prefer to use lower molecular weight white mineral oils having viscosities which lie within the range of from about 55 to 90 Saybolt Seconds Universal (SSU) at 100 F. Most preferred are those white mineral oils having a viscosity of between 55 to 65 S.S.U. 'at 100 F. In terms of specific gravity, such oils lie in the range of from .837 to 854 at 60 F., and, preferably, Within the range of from .837 to .847 at 60 F. Particularly good results have been obtained with the white mineral oil, a refined petroleum oil sold by the Pennsylvania Refining Company under the trade name, Drakeol 6. I

The amount of mineral oil present in our therapeutic compositions is not narrowly critical and can vary over a wide range. Thus, we have prepared therapeutic compositions containing from about 68 to about 97 percent by weight of mineral oil, but prefer that the mineral oil component be present in such compositions in amounts ranging from about 75 to about 85 percent by weight. Best results appear to be obtained when our compositions contain about 81 percent by weight of mineral oil.

We can employ any microcrystalline petroleum wax, in our novel therapeutic compositions. The preferred waxes can be generally defined as having a melting point in the range of from about 170 to about 195 F. Typical of such microcrystalline waxes is the product sold by the Bareco Wax-Company (a division of Petrolite Corporation), under the trade name Be Square and of the grade 190/ 195 White. The amount of rnicrocrystalline wax employed is not narrowly critical and can vary over the range of from about 0.1 to 2 percent by weight of our composition. In most instances, however, we prefer to employ the wax in an amount equivalent to 1 percent by weight of the therapeutic composition.

The preferred dispersing agents used in our novel compositions include, for example, the fatty acid esters of polyhydric alcohols. They are prepared, as their name well demonstrates, by the esterification of a fatty acid with a polyhydric alcohol. In many instances they are termed surface active agents, and include such non- 'toxic materials as diethylene glycol monolaurate, glycerol oleate, and the like. We prefer that such fatty acid esters be soluble in the mineral oil employed in our novel compositions, and to this end, a desirable class of such esters are those partial fatty acid esters of cyclic ether alcoholssuch as the'sorbita-n oleate products manufactured and sold by the Atlas Powder Company under the trade name Span 80. Operable also are those mineral oil soluble polyoxyethylene substituted fatty acid esters of polyhydric alcohols [Tweens (65 and 81) and Spams-tradenames]; More particularly, Tween 65 and 81 are respection is not capable of providing the activity described. In this respect, and insofar as We can determine, the combined ingredients of our novel therapeutic compositions appear to act or react in some sort of synergistic manner.

The unique capacity of the therapeutic compositions of our invention to provide relief from distress caused by the accumulation and adherence of gas in and to the walls of the gastrointestinal system is perhaps best illustrated, in a relative sense, by referring to a series of studies carried out in connection with a highly-foamable water system. In these studies there was measured the ability of various compositions (both within and without the scope of the present invention) to reduce the tendency of such systems to entrap air upon agitation, and, thereafter, determining the capacity of these same compositions to release air which actually become entrapped in the aforesaid systems during agitation. Since air entrapment in the system under investigation manifests itself in the form of foam, there was'employed the relative volume of foam produced after agitation as a measure of the extent to which a given composition tends to reduce air-entrapment. The capacity of these same compositions to release entrapped air was determined by allowing the agitated system to stand, and, thereafter, noting the difference in foam volumes. The procedure followed in these studies included the steps of adding a predetermined amount of a given composition to a one-hundred milli liters (100) glass stoppered graduated cylinder containing fifty milliliters (50) of'a one percent water solution of an anionic, high-foaming, surface active agent, sealing the cylinder, and finally shaking the resulting system thirty (30) times by hand. At this point, the volume of foam produced, in excess of the original liquid level, was measured and noted, and the agitated system was then allowed to stand for a period of ten (10) minutes. Measurements of foam volume remaining in the system were takenat periods of five (5) and ten (10) minutes. The surface active agent employed was an alkyl aryl sulfonate manufactured and sold by the Atlantic Refining- Company under the trade name Ultrawet L. More particularly, this mark identifies a series of surface-active agents containing aromatic monosodiurn sulfonate with or without the addition of sodium sulfate. 7

The compositions evaluated in these studies are fully described in the table below. Those compositions which fall within the scope 'of our invention were prepared in accordance with methods commonly followed in obtaining mixtures of two or more ingredients of the type employed. For comparative purposes we employed a foamable water system free of any added composition as a control. The data concerning this control are carried unde the heading indicating foam volumes resulting from the use of Composition No. 15 and, for the purposes of completeness, this composition has been identifiedand carried as a blank within Table I below.

TABLE I.FORMULATION OF VARIOUS COMPOSITIONS EVALUATED IN VIIRO FOR TREATMENT INTESTINAL GAS AND BLOATING Constituent Composition Nos.

Mineral Oil 94. 0 86. 0 100. 0

Microerystalline Wax- 1. 0 1. 0 Dispersing Agent. 5. 0 Magnesium Stearate..- 13. 0 Aluminum Stearate. c

Calcium Stearate I Zinc Stearate c tow-ards providing the unique antifoaming activity described hereinbefore, inasmuch as omission of any one ingredient has demonstrated that the resulting composi- In the initial studies reported within the tabulated data,

one drop (25 to 30 mgs.) of each of the compositions (Table I) was employed towards testing their ability to reduce the tendency of the system to entrap air, and, thereafter, there was determinedthe ability of these compositions to release and inhibit that air which became entrapped in the system as a consequence of being agitated. The resulting data appear in Table II below.

TABLE II.-ABILITY OF ONE DROP OF THE COMPOSI- TIONS DESCRIBED IN TABLE I TO REDUCE AIR ACCU- MULATION IN WATER SOLUTIONS OF A FOAMING A GENT Foam Volume Above Original Liquid Level (milliliters) After Composition Thirty Standing For Standing For Agitations Five Minutes Ten Minutes 31. 15. O 8. O 60. 0 52. 0 52. 0 43. 0 40. 0 39. 0 40. 0 35. 0 35. 0 45. 0 39. O 33. 0 40. 0 25. 0 20. 0 30. 0 21. 0 17. 0 48. O 45. 0 35. 0

1 Foam volume reached top of graduate and no movement of liquid could be determined during agitation.

2 No change in volume or nature of foam.

The data reported above readily illustrate the unique ability of our therapeutic compositions to reduce the extent to which air is normally entrapped in an agitated foamable water solution. Moreover, as evidenced by the marked decrease in foam volume, upon standing, of those systems containing our novel compositions (Nos. 1 through 7 and 16 through 19) are characterized by a significant capacity to cause release of entrapped air. The data obtained are of further importance as they clearly illustrate the synergistic effect provided by the four (4) components of our compositions in releasing air entrapped in these systems, as contrasted, for example, with the silicones, per se, among other known systems alleged to produce the same results.

Further studies were then carried out along the lines described for the above evaluation, but with the exception that three drops (approximately 75 mgs.) of each composition, described in Table I, were added to the foamable Water system. The data obtained in these studies appear in Table III below:

TABLE TIL-ABILITY OF THREE DROPS OF THE COMPO- SITIONS DESCRIBED DI TABLE I TO REDUCE AIR ACCU- Mg$ION IN WATER SOLUTIONS OF A FOAMING A I Foam Volume reached top of graduate and no movement of liquid could be determined during agitation.

2 N 0 change in volume or nature of foam.

The above data more vividly illustrate the unique and remarkable capacity of our novel therapeutic compositions to significantly reduce the extent to which air becomes and remains entrapped in agitated water solutions of foaming agents. With respect to this particular foam producing system, these data suggest that a more eficctive reduction of initially entrapped air (as evidenced by lower initial foam volumes) and a more rapid release of entrapped air (as evidenced by lower ultimate foam volumes) is obtained by use of our compositions in amounts greater than one drop. To a more significant extent than that illustrated in Table H, these data show the synergistic improvement provided by the components of the novel compositions. Thus, for example, Composition No. 11 which comprises only mineral oil, Composition No. 12 which comprises mineral oil and sorbitan oleate and Composition No. 14 which comprises mineral oil and microcry-stalline wax all exhibit little or no tendency (as compared to the control system of Composition No. 15) to reduce the amount of air initially entrapped or to cause release of entrapped air in such systems. The same can be said for Composition No. 9 which comprises mineral oil, microcrystalline wax and sorbitan oleate, while Composition No. 10 which comprises mineral oil, microcrystalline wax and magnesium stearate, Composition No. 13 which comprises mineral oil and magnesium stearate and Composition No. 8 which comprises mineral oil, sorbitan oleate and magnesium stearate, exhibit considerably less capacity to reduce initial foaming and cause foam reduction than Composition No. 1 (a preferred embodiment of our invention). Similar observations would result with respect to those preferred embodiments of Compositions Nos. 2 through 4, when compositions, in which calcium, zinc, and aluminum stearate are substituted for the magnesium stearate of Compositions 8, 10, and 13, are prepared and evaluated.

In an efiort to determine optimum concentrations of our compositions in foamable water systems, there was carried out a third study in much the same way as that described for the previous work, with the exception that five (5) drops (approximately 125 milligrams) of each composition described in Table I were employed. The data from this study appear in Table IV set forth below:

TABLE IV.ABILITY OF FIVE DROPS OF THE COMPOSI- TIONS DESCRIBED IN TABLE I TO REDUCE AIR ACOU- MULATION IN WATER SOLUTIONS OF A FOAMIN G AGENT Foam Volume Above m1. (milliliters) After- Composition Thirty Standing For Standing For Agitations Five Minutes Ten Minutes Foam volume reached top of graduate and no movement of liquid could be detenniued during agitation.

Z N 0 change in volume or nature of foam.

The data reported in Table IV above, further illustrate l the unique and remarkable capacity of our novel therapeutic compositions to reduce the amount of air normally entrapped in the systems under study and, at the same time, provide additional evidence of their unique tendency to cause a reasonably rapid release of that air which became entrapped in these systems during agitation. Moreover, the synergism provided by the combination of components which comprise our novel compositions is again clearly proven.

Our novel compositions may also contain other active ingredients which exhibittherapeutic activity and thereby provide various embodiments of the present invention capable of multifunctional, and perhaps synergistic, utility in the treatment of gastrointestinal disorders. By way of illustration, one class of active ingredients which we have intestinal absorbents are certain innocuous clays, which 1 generally comprise one or more of the naturally occurring hydrates and mixed hydrates of magnesium or aluminum silicate, such as kaolin, halloysite and attapulgite, and certain synthesized metal hydrates such as the calcium and magnesium silicates prepared by precipitation or hydrothermal techniques. Another class of active ingredients which wehave found extremely useful to employ in combination with our therapeutic compositions are those alkaline agents, generally referred to as antacids, that serve to alleviate discomfort caused by the hyperacidity of certain gastric fluids. These antacids include suchmaterials as alumina gel, magnesium oxide, magnesium hydroxide, urea, sodium bicarbonate, sodium carboxymethylcellulose as well as mixtures thereof and the like. Similarly, other classes of active ingredients including antispasmodics, analgesics, antibiotics, sedatives and the like may be incorporated within our compositions to provide additional relief fromdi'stress of the gastrointestinal system. When added to our compositions, the active ingredients are generally employed in amounts which can vary over the ranges usually employed for their intended purposes.

The therapeutic compositions of this invention are intended for oral administration and, to this end they may take various physical forms as for example, liquid suspensions, gels, powders, tablets and capsules. Preparation of our therapeutic compositions may be accomplished by various admixing procedures, well known in the art, which are appropriate for the physical form desired. Depending on the form selected, it will oftentimes be desirable to add ingredients of the non-therapeutic type which conveniently serve to adapt our novel compositions for a specific purpose. Thus, for example, preservatives such as sodium benzoate and sorbic acid, as well as other comparable materials can be employed when preparing aqueous liquid suspensions of our compositions. In the preparation of tablets, the use of one or more binders and lubricants is suggested to provide proper characteristics. Flavoring agents such as sorbitol and citric acid, and coloring agents can also be employed to render our compositions more appealing, should such be deemed necessary in their administration to those who have an aver sion to medication. When incorporated within our novel compositions, such non-therapeuticiadditives are employed in amounts consistent with the specific functions they serve.

The basic principles of the invention will be more fully described with respect to a specific therapeutic composition and certain formulations containing this composition in combination with other therapeutically active and non-active additives, which, however, is in no way to be considered as limiting the overall scope or utility 8 of our discovery. In accordance with the foregoing, the following examples are provided to illustrate the unique and remarkable capacity of our novel compositions to provide relief from distress caused by the accumulation and adherence of gas in and to the walls of the gastrointestinal system.

'In the foregoing connection, it is postulated that our unique gastrointestinal defoamer functions as an entity of its four individual components when mixed together in a definite sequence and under specific conditions. To re-' iterate, the four components of the system are (1) a white mineral oil, (2) a metallic soap, (3) microcrystalline wax and (4) a dispersing agent. Individually, these ingredients do not exhibit any defoaming characteristics.

Additionally, even when two or three of the above ingredients are utilized together, the defoarning ability isnot comparable in any way to the total efiect of the four component system. It is theorized that when all four components are compounded in a homogenous mixture by the method described in Example I, to illustrate, various physicochemical phenomena occur. The white mineral oil functions as a carrier for the other ingredients and, having a lower specific gravity than Water, will float and spread over the surface of aqueous media. The metallic soap is polar in nature, composed of a hydrophyllic metal and a fatty acid which is hydrophobic. The fatty acid portion of the metal soap, due to its oil solubility, will orient the molecule at the inter-face of the white mineral oil with water. Microcrystalline wax is used because it is only soluble in the mineral oil when hot, and upon cooling will crystallize out of the solution in definite patterns. When the defoamer is compounded as in Example I, the

microcrystalline wax is dissolved hot in a small portion of the mineral oil and allowed to crystallize on the already dispersed metallic soap, thereby making the soap more hydrophobic than it was originally, and also orienting it so that in a thin layer of oil the hydrophobic part of the soap molecule is directed towards the inside and the hydrophyllic part towards the outside of the layer. Thecorn bination of metal'soap and microcry-stalline wax in the White mineral oil is so hydrophobic that an appropriate oil soluble dispersing agent has to be used in order to obtain sufiicient spreading action to facilitate the formation of a thin molecular film at the inter-face of the aqueous solution and around the gas bubbles-It is assumed that due to the high degree of orientation of the metallic soap particles in the oil, bursting of :the foam bubbles occurs on contact with the hydrophyllica-lly oriented surface of the mineral oil film. It should also be noted that the.

In the application of the foregoing postulated mechanism within the human or animal organism, it 'is assumed that within the gastrointestinal tract where foams may adhere to the lining, the spreading effect of our unique defoamers over the aqueous surface .of-the gas bubbles will not only function to rupture or break'the bubbles, but

also to separate and push them away from the intestinal wall.

EXAMPLE I Preparation of therapeutic composition A therapeutic composition comprising an intimate mixture of magnesium stearate, mineral oil, microcrystalline wax and sorbitan oleate was prepared by first adding 61 parts by weight of white mineral oil (N.F. grade), having a viscosity of 60 S.S.U. at F.,to a beaker equipped with a high speed agitator. About 5 parts by weight of V sorbitan oleate was then added to the beaker and the agitator was started and set at medium speed. At this point, about 13 parts by weight of magnesium stearate (F.G.) was slowly added to the mixture, and agitation was continued. Thereafter, in a separate beaker 1 part by Weight of microcrystalline wax, having a melting point between 190 to 195 F., was dissolved in 20 parts by weight of white mineral oil (N.F. grade) at a temperature of 160 F. The hot solution was added to the mixture and agitation was continued until a fine dispersion was obtained upon cooling.

EXAMPLE 11 Evaluation and comparison of therapeutic compositions A simulated gastrointestinal system, which provides an in vivo environment, was devised by placing a 250 ml. graduated cylinder containing 50 ml. of Gastric Juice T. S. (U.S.P.) and a small amount of food stuff, in a water bath maintained at the normal body temperature of 37 C. To illustrate, in a somewhat exaggerated manner, the effect of gas in this system by the resulting accumulation and adherence of entrapped gas in and to the walls thereof, we provided a source from which air, at a pressure of 25 p.s.i., could be bubbled into the mixture of gastric juice and foodstuffs. For purposes of comparison, two additional graduated cylinders were provided in the water bath in order to simultaneously evaluate the therapeutic composition of Example I and a commercially available silicone antifoam (suggested for use in overcoming intestinal gas and bloating) against a control which contained no additive. A considerable number of simulated conditions, often found in the gastrointestinal system, as for example, mixtures of gastric juice and various foodstuffs such as evaporated milk, gum arabic, sucrose, starch, eggs, mayonnaise, and gastric mucin, were examined to provide a broad base for our evaluation. Moreover, it was believed that such conditions would closely resemble those which cause accumulation and adherence of gas in and to the walls of the gastrointestinal system. For convenience of reference, Gastric T. S. (U.S.P.) can be prepared by dissolving 3.2 grams of pepsin (110,000) in approximately 500 milliliters of water and adding seven milliliters of concentrated hydrochloric acid together with two grams of sodium chloride. Solutions of suitable concentrations for our needs were obtained by diluting this preparation to 1000 milliliters.

This evaluation was carried out by adding specified amounts of our therapeutic composition and the commercially available silicone antifoam preparation to two of the mixtures being studied and thereafter bubbling air through all three of the mixtures for a period of one minute. By following this procedure we could determine the tendency of each mixture to entrap air and the relative efiect of such entrapment in much the same way, as that which, but to a much lesser degree, takes place when air is swallowed or gases are produced under similar conditions in the gastrointestinal system of warm-blooded animals. Since air entrapment in these mixtures produces foam, we used the volume of foam produced in the control as a measure of that mixtures natural tendency to entrap air, while the volume of foam produced in the other two mixtures was taken as a measure of the ability of the silicone anti-foam and of our composition to alter this tendency. By permitting the air-treated control to stand for periods of from one to five minutes, We could determine the rate at which that mixture normally releases entrapped air by simply measuring the amount of foam remaining at that time. Similarly, by permitting the other two mixtures to stand for like periods and measuring the volume of foam remaining at that time, we could determine the capacity of the silicone antifoam and of our novel compositions to alter the rate at which entrapped air is released. The data thus obtained appear in theTables V-XI below.

TABLE V.EFFECTIVENESS OF THE THERAPEUTIC COMPOSITION OF EXAMPLE I AND A SILICONE ANTI- FOAM PREPARATION IN REDUCING GAS ACCUMULA- TION IV A MIXTURE COMPRISING 50 ML. OF GASTRIC JUICE AND 20 ML. OF EVAPO RATED MILK (A) Approximately 25 mgs. (1 drop) of each added Foam Height in ml. Above Control Composition Silicone Original Level Alterof Example I Antitoarn 1 Minute of Bubbling Over top.. 6 125 1 Minute of Standing 4 18 Five Minutes of Standing 4 14 (B) Approximately 75 rugs. (3 drops) of each added 1 Minute of Bubbling Over top 2 30 1 Minute of Standing 2 3 Five Minutes of Standing 2 2 (C) Approximately 125 mgs. (5 drops) of each added 1 Minute of Buhbling Over top 6 1 Minute of Standing. 3

Five Minutes of Standing 2 TABLE VI.--EFFECTIVENESS OF THE THERAPEUTIC COMPOSITION OF EXAMPLE I AND A SILICONE ANTI- FOAM PREPARATION IN REDUCING GAS ACCUMULA- TION IN A MIXTURE COMPRISING 50 ML. OF GASTRIC JUICE AND 20 ML. OF A 20% SOLUTION OF GUM ARABIC IN WATER (A) Approximately 25 mgs. (1 drop) of each added Foam Height in ml. Above Control Composition Silicone Original Level Aiter of Example I Antiioam 1 Minute of Bubbling Over top Practically 1 Minute of Standing 4 Five Minutes of Standing-.- 2

(B) Approximately 75 mgs. (3 drops) of each added 1 Minute of Bubbling Over top.. Practically 24.

none. 1 Minute of Standing None 2. Five Minutes of Standing". o Practically none.

(C) When concentrations were raised to mgs. (5 drops), both the composition of Example I and the silicone antifoam were efiective in completely eliminating foam.

TABLE VII.EFFECTIVENESS OF THE THERAPEUTIC COMPOSITION OF EXAMPLE I AND A SILICONE ANTI- FOAM PREPARATION IN REDUCING GAS ACCUMULA- TION IN A MIXTURE COMPRISING 50 ML. OF GASTRIC JUICE AND 20 ML. OF A 50% SOLUTION OF SUCROSE =IN IVATER (A) Antiioam concentration equal approximately 25 rugs. (1 drop) of (C) When concentrations were raised to approximately 125 mgs. (5 drops) both the composition of Example I and the silicone antitoam were effective in completely eliminating foam.

TABLE VIIL-EFFECTIVENESS OF THE THERAPEUTIC COMPOSITION OF EXAMPLE I AND A SILICONE ANTI- FOAM PREPARATION IN REDUCING GAS ACCUMULA- TION IV A MIXTURE COMPRISING 50 ML. OF GASTRIC JUICE-3 AND ML. OF A 10% SOLUTION OF STARCH IN WAT R.

TABLE XI.EFFECTIVENESS OF THE THERAPEUTIC COMPOSITION OF EXAMPLE I AND A SILICONE ANTI- FORM PREPARATION IN REDUCING GAS ACCUMULA- TION IN AMIX'IURE COMPRISING 50 ML. GASTRIC JUICE %?PI20RML. OF A 10% SOLUIION OF GASTRIC MUCIN IN (A) Approximately 25 mgs. (1 drop) of each added (A) Approximately 25 mgs. (1 drop) of each added Foam Height in ml. Composi- Silicone Foam Height in mi. Composi- Silicone Above 70 ml. After Control tion of Antifoarn Above 70 ml. After Control tlon of Antiioam Example I Example I 1 Minute of Bubbling Over top None 20. 1 M nute of Bubbling 90 30 llMinute of Standing ....do Practically 1MinuteofStanding.. 30 6 26 none. Five Minutes of Standing; 30 4 18 Five Minutes of Standing--. ..do None.

(B) Approximately 75 mgs. (3 drops) of each added (B) Approximately 75 mgs. (3 drops) of each added 1 1 Minute of Bubbling 90 Practically 10 1 Minute 0; ublalling Over top... t u 1 Minute of Standing 30 11051:. 4 1 \l' t t rac ca e l um 80 an Hg y Five Minutes of Standing... 30 ...do.... 2 Five Minutes of Standing... None.

(0) Approximately 125 mgs. (5 drops) of each added (0) Rising concentralliions of each additive to 125 nigs. (5 drops) elimin- 1 t ated {0am e e y 1 Minute of Bubbling 90 None..-...-- 10 1 Minute of Standing. 5 Five Minutes of Standin 2 TABLE IX.EFFECTIvENEss OF THE THERAPEUTIC COMPOSITION OF EXAMPLE I AND A SILICONE ANTI- FOAM PREPARATION IN REDUCING GAS ACCUMULA- TION IN A MIXTURE COMPRISING 50 ML. OF GASTRIC JUICE AND 20 ML. OF WHOLE EGGS As is readily apparent from the above data, consider- (A) Approximately 25 mgs. (1 drop) of each added able amounts of air became entrapped in the control mixtures as evidenced by the degree to which foam was pro- Foam Height in mi. Composi- Silicone duced. In practically all instances, except where mayon- AbWB 70 Afier gg I Antlioam naise and gastric mucin were employed as the foodstuff, foaming occurred to the extent of flowing over the top lMmute Bubbling Over 2 Overtm of the 259 milliliter glass graduate. With these same ex- 1 Minute ofStanding 2 26. ceptions, It should be noted that the volume of foam re-' Mmutes MSmndmgn- 2 'maining in the graduate was not materially reduced by simply allowing the control mixtures .to stand for periods (B) Approxmlately 75 (3 amps) each added up to five minutes. By way of comparison, our data con- 40 firm prior findings that silicone antifoams are useful in 1 Mmute OfBubbhng Over igfg Over reducing the amount of air initially entrapped in the gas- 1 Minute of Standing- None 28. me mice mixtures employed and, in addition, are helpful Mmutes MSmmmgm in releasing entrapped air when such mixtures are al-' d h M d lowed to stand. However, certain important observations (C)Appmumate1yl25mgs (5 mp5) a e must be made with respect to the degree of elfectivencss f bu O N O t exhibited by such silicone antifoarns. Generally speaking, g g g g one with only a few exceptions, at lower concentrations Five Minutes ofStandiiN.-. 10. silicone antifoams do not reduce the amount of an initially entrapped in gastric juice mixtures, under the conditrons employed, to particularly low levels, such as those evidenced by foam volumes (after bubbling) of less than 20 ml. Moreover, in many instances, such as those in n E W N SS OF T APE 10 which evaporated milk (Table V), whole eggs (Table TABLE X.EFF CT E E THE HER UT r COMPOSITION OF EXAMPLE I AND A SILICONE ANTI- f gasmc a l XI) f the foodstflfi rpg /r i n pi r t p a 'plgg gvfi lggggg pas additives, one drop of the silicone antifoam preparation Z 1 20 ML OF A A was not suflicient to provide a reasonably rapid release (A) Approximately 25 (1 drop) ofeach added of entrapped air from the standing mixtures. Better, al-

though not entirely satisfactory, results were obtained Foam Height in ml. Composi- Silicone when the concentration of silicone antifoam in the mix-1 Above .70 After Control gg fig I Antlfoam tures was increased to 75 mgs. Inasmuch ,as improvement in reduction of foam volumes was generally Observed with lMimlte Bubbling 40 6": m a further increase In concentration of silicone antifoam 1 Minute oiStand1ng 2 Practically 10. (to 125 mgs.), we concluded from the nature of the data DOUG. Five Minutes Standing 2 None Practically obtained that at least this amount of the antifoam is gennon erally required to satisfactorily treat mixtures of gastric uices and foodstuffs. (B) Appmxlmately 75 (3 amps) of each added Clearly shown by the data reported in Tables V through X1 is the outstanding and superior capacity of o in novel VIitiBbblmg 401 tll 1i 1m e o u Y 10 therapeutic compositions to significantly reduce the lMmute of Standmg 2 g g y amount of air initially entrapped in the 'mixturesrevalu- Five Minutes of Standing.-. 2 do None. ated. Moreover, these data illustrate, in those instances where an becomes entrapped in such mixtures as a result (0) Both additives were effective in completely eliminating foam when of he bubblin IOCfiSS the uni U6 2 used at concentrations of 125 Ings. (5 drops). a p q blhty of our rfovel compositions to cause release of such entrapped tall.

13 Truly remarkable is the performance of as little as one drop of our novel compositions in reducing the foaming tendency of the gastric juice mixtures evaluated. Thus, for example, one drop of our composition is as effective as five TABLE XIII-EFFECTIVENESS OF THE THERAPEUTIC COMPOSITION OF EXAMPLE I AND A SILICONE ANTI- FOAM PREPARATION IN REDUCING GAS ACCUNIULA- TION IN A MIXTURE COMERISING 50 ML. INTESTINAL 20 ML. OF A 20% SOLUTION OF GUM ARABIC drops of silicone antifoam preparation in reducing ,air entrapment, resulting from the bubbling process, in a mix- App x m y 25 s- (1 p) of each added ture of gastric juice and evaporated milk (Table V). Furthermore, three (3) drops of our composition in this Foam Height in IE1. Composi- Silicone mixture permits the bubbling process to produce only two Abwe 70 m A W Comm gig i I Antlioam milliliters of foamthe same amount that results when a comparable mixture containing five drops of silicone lMinnte fBubbli Over None N None 1 Minute of Standing 70 0 Do. antifoam preparation is allowed to S and for five mm Five Minutes of Standing" 20 do Essentially the same observation can be made with respect to these respectlv? mammals mlxiures of gastnc Jmce (B) Higher concentrations were not tested since both compositions and a water solution of gastric mucin (Table XI). Even are very effective at concentrations M25 mgs. more dramatic are the results reported for mixtures Of gastric juice and whole eggs (Table IX) where one drop of our composition reduces air entrapment during the bubbling process to the extent that only two milliliters of foam are produced. Under similar conditions, one, three TABLE XIV.EFFECTIVENESS OF THE THERAPEUTIC COMPOSITION OF EXAMPLE I AND A SILICONE ANTI- and even five drops of slllcon fintlfoam pfepefatlon FOAM PREPARATION IN REDUCING GAS ACCUMULA- TION IN A MIXTURE COMPRISING 50 ML. OF INTEsTINAL peared to have little or no effect masmuch as foam was FLUID AND 20 ML OF A 50% SOLUTION OF SUCROSE IN produced in quantities that overflowed the graduate. In WATER addition, considerably more foam remained in those sili- A App1'0xiygate1y25mgs, (1 drop) ofeach added cone-containing mixtures after standing for five minutes than was initially produced in the mixture containing our Xgam I FIIeighIt in ml. C 1 C qm o rsilig one novel COmPGSitionS. I We 0 In terontro Exglrlipoe I nti oam The data reported for Initial air entrapment and subsequent release of entrapped air for bubbled mixtures of llx/iinute oflgubbiling 160 None Nonfi.

ll'inute ofctan ing 60 0. gastric uice with. gum arabic solutions (Table VI), su- Five Minutes cramming" 20 crose solutions (Table VIII), starch solutions (Table I VII) and mayonnaise X) further pp the (B) Highenconcentrations were not evaluated since both products unique ability of our compositions to reduce air entrap- Pwved be hlghly efiectlve at appmxlmately 25 111%- ment in simulated gastro-intestinal systems. In terms of use in warm-blooded animals, these data are illustrative of the beneficial and advantageous results provided with the aid of our therapeutic compositions in obtaining re- T1ISLPOV.(-)EFFECTIVENESISD OF THE 'I HE APEUTIC lvP ITI N OF EXAMPL AND A I ICONE ANTI- lief from distress caused by the accumulation and ad- 40 FOAM PREPARATION IN REDUCING GAS ACCUMULA herence of gas in and to the walls of the gastro-intes- TION INAMIXTURE COMPRISING sounor INT STINAL FLUID AND 20 ML. OF A 10% SOLUTION 0F sTARCH IN tmal system. WATER (A) Approximately 25 mgs. (1 drop) of each added EXAMPLE III Foam Hei ht in ml. C i- Silico e Evaluation and comparison of therapeutzc compositions Above 70 E Control $3 3? nnnfogm Example I With the aid of the apparatus described in Example II, A

I t lMinute oi Bubbling Over top None None. another group of evaluations werecarried on with respect 1 Minute of Standing 20 Do to our novel therapeutic composmons and silicone antl- Five Minutes ofStanding None .-do Do. foams in a somewhat simulated gastrointestinal environment. On this occasion, we employed Intestinal'Pluid T. S. l lie gr g e t g s w not evaluated since both compositions (U.S.P.) as the basic medium and added the same foodprove 0 e y e at appmxlmmly 25 stuffs thereto to provide new mixtures for our comparative evaluations. In all other respects, the procedures followed were the same as described in Example II. The data obtained are resented in tabluated form below within 'TABLE XVI.-EFFECTIVENESS OF THE THERAPEUTIC COMPOSITION OF EXAMPLE I AND A SILICONE ANTI- Tables XII through XVIII- FOAM PREPARATION IN REDUCING GAs ACCUMULA- TION IN A MIXTURE COMPRISING 50 ML. OF INTESTINAL FLUID AND 20 ML. OF WHOLE EGGS (A) Approximately 25 mgs. (1 drop) of each added TABLE XII.EFFECTIVENESS OF THE THERAPEUTIC COMPOSITION OF EXAMPLE I AND A SILICONE ANTI- Foam Hmsht 111 Q P 511190119 FOAM PREPARATION IN REDUCING GAS ACCUMULA- Above 70 Control twn 0f Antifoam TION IN A MIXTURE COMP RISING 50 ML. OF INTEsTINAL Example I FLUID AND 20 ML. OF EVAPORATED MILK (A) Approximately25 mgs. (1 drop) of each added 1 Minute of Bubbling Over top 10 Over top.

1 Minute of Standing 6 Five Minutes of Standing... 4 Foam Height in ml. Composi- Silicone Above ml. After Control tion of Antifoam Example I (B) Approximately mgs. (3 drops) of each added 70 minute of Bubbling Over top 20 10 1 Minute of Bubbling Over top.. 2 Over top. 1 Minute of Standing.-- 2 None 1 Minute of Standing 2 Five Minutes of Standing--. 2 None Five Minutes of Standing 2 (B) Raising concentration of each additive to 75 mgs. (3 drops) eliminates loam completely.

(C) Results for mgs. (5 drops) of each composition were exactly the same as for 75 mgs. (3 drops).

TABLE XVII.-EFFECTIVENESS OF THE THEREAPEUTIC COMPOSITION OF EXAMPLE I AND A SILICONE ANTI- FOAM PREPARATION IN REDUCING GAS ACCUMULA- TION IN A MIXTURE COMP RISING 50 ML. OF INTESTINAL FLUID AND 20 ML. OI MAYONNAISE (A) Approximately 25 mgs. (1 drop) of each added Foam Height in ml. Composi- Silicone Above 70 ml. After Control tion of Antitoam Example I 1 Minute of Bubbling 80 8 20 1 Minute of Standing 20 4 18 Five Minutes of Standing.-- 20 4 (B) Approximately 75 mgs. (3 drops) of each added 1 Minute of Bubbling 80 Practically 10 none.

1 Minute of Standing 20 None 6 Five Minutes of Standiug 20 o. 4

(C) When concentrations were raised to approximately 125 mgs. (5

drops), both compositions completely eliminated foam.

TABLE XVIII.EFFECTIVENESS OF THE THERAPEUTIC COMPOSITION OF EXAMPLE I AND A SILICONE ANTI- FOAM PREPARATION IN REDUCING GAS ACCUMULA- Formulation ATablets.The composition of Example I and calcium silicate (an intestinal absorbent) were combined by adsorbing 4.9 grams of the former onto 2.1 grams of the latter, and the product dry-blended with 43.0 grams of lactose. Tablets of 0.5 grams and containing 50 mgs. of the composition of Example I were compressed from the resulting mixture.

Formulation B-Liquid suspension.To a beaker were added 100 ml. of a liquid antacid containing calcium car- 0 bonate and urea in the ratio of 7 parts of the former to 3 each containing mgs. of the composition of Example'I.

Formulation D-Tablets.About 2.5 grams of the composition of Example I were blended with 87.4 grams of a mixture of urea, and calcium carbonate in a ratio of 3 to 7. Small amounts of lubricants and binders were 25 added and the mixture was compressed into tablets each TION IN A MIXTURE COMPRISING 50 ML. OF INTESTI- NAL FLUID AND 20 ML. OF A 10% SOLUTION OF GASTRIC MUCIN I WATER (A) Approximately 25 mgs. (1 drop) of each added Foam Height in ml. Composi- Silicone Above 70 ml. After- Control tion of Antifoam Example I 1 Minute of Bubbling 60 6 110 1 Minute of Standing 50 2 60 Five Minutes of Standing 25 2 50 (B) Approximately 75 mgs. (3 drops) of each added 1 Minute of Bubbling (i0 Practically 80 none.

1 Minute of Standing 50 None 60 Five Minutes of Standing 25 do 50 (0) Approximately 125 mgs. (5 drops) of each added 1 Minute of Bubbling- 50 1 Minute of Standing Five Minutes of Stand 30 Many of the same observations made in connection with the relative efficacy of silicone antifoams and our novel compositions in reducing air entrapment in, and in causing release of entrapped air from, gastric juice mixtures can be made with respect to the intestinal fluid evaluations reported in Tables XII through XVIII above. Particularly noteworthy is the capacity of our composition to remarkably reduce air entrapment in mixtures of intestinal fluid and gastric mucin (Table XVIII). One drop of our composition results in considerably less air entrapment, as measured by volume of foam produced, than that which results from the use of five drops of silicone antifoameven after such mixtures have been permitted to stand for a period of five minutes. In terms of use in warm-blooded animals, these data are further illustrative of the unexpected and beneficial results provided through use of our unique compositions towards provid- 'ing relief from distresses caused by the accumulation and adherence of gas within the gastrointestinal tract.

EXAMPLE 1V Preparation and evaluation of various forms of novel therapeutic compositions In accordance with the teaching of the present invention, the following formulations were prepared.

containing 25 mgs. of the composition of Example I.

Following the procedure described in Example II and using the apparatus described therein, Formulations A through D were evaluated in terms of their ability to re- 30 duce air entrapment in various mixtures of gastric juice and intestinal fluid. In addition, they were evaluated in terms of their capacity to release entrapped air from such mixtures. The data obtained are presented in Tables XD( through XXII below, and are compared with the results obtained from a control, as well as with the results obtained from the use of Composition I of Example I.

40 TABLE XIX.COMPARATIVE EFFECTIVENESS OF THE COMPOSITION OF EXAMPLE I AND THOSE FORMULA- TIONS OF EXAMPLE IV WHICH CONTAIN SAID COMPOSI- TION IN REDUCING GAS ACCUMULATIONIN AMIXTURE COMPRIXING 50 ML. OF GASTRIC .IUICE AND 20 ML. OF EVAPORATED MILK Foam Volume Above ml. (ml.) After- Formulation One Min. One Min. Five Min. of Bubbling of Standing of Standing Control Over top No change No change. Example I 22 4 2. A 4 2 2.

B 1 Practically None. none.

C 70 2. D 20 Practically None.

none.

TABLE XX.COMPARATIVE EFFECTIVENESS OF THE COMPOSITION OF EXAMPLE I AND THOSE FORMULA- TIONS OF EXAMPLE IV WHICH CONTAIN SAID COMPOSI- TIONIN REDUCING GAS ACCUMULATIONIN A MIXTURE COMPRISING 50 ML. OF GASTRIC JUICE AND 20 MIL. OF WHOLE EGG TABLE XXI.-COMPARATIVE EFFECTIVENESS OF THE COMPOSITION OF EXAMPLE I AND THOSE FORMULA- TIONS OF EXAMPLE IV WHICH CONTAIN SAID COMPO- TABLE XXII.-CO1V1'.PARATIVE EFFECTIVENESS OF THE COMPOSITION OF EXAMPLE I AND THOSE FORMULA- TIONS OF EXAMPLE IV WHICH CONTAIN SAID COMPO- SITION IN REDUCING GAS ACCUMULATION IN A MIXTURE COMPRISHIG 50 ML. OF INTESTINAL FLUID AND 20 ML. F WHOLE EGG Foam Volume Above 70 ml. (1131.) After Formulation One Min. One Min. Five of Bubbling of Standing of Standing Control- Over top No change No change Example I 10 6 2 A 80 70 60 B 15 11 5 C 80 40 38 D 160 140 110 The data reported above in Tables XDi through XXII generally illustrate that our novel compositions can be used with other active therapeutic ingredients to provide formulations having multiple utility in the treatment of gastrointestinal disorders. Of importance in this evaluation is the observation that while the ability of these formulations to reduce initial air entrapment may be somewhat lessened (as compared to Compositions I per se), such formulations appear to be characterized by an increased capacity to cause release of air, once it has become entrapped in the mixture. Thus, these formulations are suitable for use in warm-blooded animals to provide relief from distress caused by the accumulation and adherence of gas in and to the walls of the gastrointestinal system, including, for example, bloat in animals, as well as from other disorders thereof, such as hyperacidity and the presence of other causative substances. In such applications within warm-blooded animals, in general, it is found that the dosage level may vary from between 0.025 to grams. For human therapy, per se, the preferred dosage level will usually vary between 0.025 to 1 gram, whereas the dosage indication used in the treatment of animal disorders such as bloat and the like, preferably varies from between 0.5 to 2 grams. The higher unit dosage levels (i.e., up to 10 grams) are generally employed when the compositions are administered to the afilicted host or animal in the 18 form of a feed additive or thelike, under which circumstances not all of the therapeutic dosage can be expected to be consumed by the animal. On the other hand, however, the compositions are totally non-toxic and even increased dosage levels would not be harmful.

Having thus described the subject matter of our invention, What it is desired to secure by Letters Patent is:

1. A therapeutic composition capable of provi iing relief from distress caused by the accumulation and adherence of gas in and to the walls of the gastrointestinal system which comprises from about 5 to about 20 percent by weight of a metal soap selected from the group consisting of magnesium stearate, calcium stearate, zinc stearate and aluminum stearate, from about 0.1 to about 2 percent by weight of a microcrystalline wax having a melting point in the range of from about 170 F. to about 195 F., from about 68 to 97 percent by weight of white mineral oil having a viscosity in the range from about 55 to about Saybolt Seconds Universal at 100 F. and from about 1 to about 10 percent of a dispersing agent selected from the group consisting of fatty acid esters of glycols, glycerol and sorbitol and polyoxyethylene substituted fatty acid esters of polyhydric alcohols.

2. The therapeutic composition of claim 1 in which said mineral oil has a viscosity in the range of from about 55 to about 65 Saybolt Seconds Universal at 100 F.

3'. The therapeutic composition of claim 1 in which said dispersing agent is sorbitan oleate.

4. A therapeutic composition capable of providing relief from distress caused by the accumulation and adherence of gas in and to the walls of the gastrointestinal system which comprises:

(a) the composition of claim 1, and

(b) an intestinal absorbent.

5. The composition which comprises:

(a) the ingredients of claim 1, and

(b) an antacid.

6. The composition which comprises:

(a) the ingredients of claim 1, and

(b) an antacid comprising calcium carbonate and urea.

7. The therapeutic composition, in tablet form, which comprises:

(a) the ingredients of claim 1, and

(b) an antacid comprising glycine and calcium carbonate.

8. A therapeutic composition capable of providing relief from distress caused by the accumulation and adherence of gas in and to the walls of the gastrointestinal system which comprises about 1-3 percent by weight of magnesium stearate, about 1 percent by weight of a microcrystalline wax having a melting point of from about F. to about F., about 81 percent by weight of a White mineral oil having a viscosity of about 60 Saybolt Seconds Universal at 100 F. and about 5 percent by weight of sorbitan oleate.

9. A method of treating gastrointestinal distress by the accumulation and adherence of gas in and to the walls of the gastrointestinal system of a warm blooded animal which comprises orally administering to said animal an effective amount of a composition comprising from about 5 to about 20 percent by weight of a metal soap selected from the group consisting of magnesium stearate, calcium stearate, zinc stearate and aluminum stearate, from about 0.1 to about 2 percent by weight of a microcrystalline wax having a melting point in the range from about 170 F. to about 195 F., from about 68 to 97 percent by weight of a white mineral oil having a viscosity in the range from about 55 to about 90 Saybolt Seconds Universal at 100 F. and from about 1 to 10 percent by weight of a dispersing agent selected from the group consisting of fatty acid esters of glycols, glycerol, and sorbitol and polyoxyethylene substituted fatty acid esters of polyhydric alcohols.

10. The method of claim 9 in which said mineral oil .has a viscosity in the range of from about 55' to about 65 Saybolt Seconds Universal at 100 F. i 7

llgThe method of claim 9 in which said composition .is' orally administered at a unit dosage level between from 0.025 to 10 grams.

7 References Cited 7 UNITED STATES PATENTS 8/1951 McGinn 1;; 252358 20 OTHER REFERENCES Quin, A. H. et al.: A New Appioach to tlieiTreatment of Bloat in Ruminants, J. Amer. Vet. Medical Assn. (May 1949), p. 313. I V

ALBERT T. MEYERS, Prinmry Examiner.

-S. ROSEN, Examiner.

S. I. SINGER, V. C. CLARK-E; Assistant Examiners. 

1. A THERAPEUTIC COMPOSITION CAPABLE OF PROVIDING RELIEF FROM DISTRESS CAUSED BY THE ACCUMLATION AND ADHERENCE OF GAS IN AND TO THE WALLS OF THE GASTOROINTESTINAL SYSTEM WHICH COMPRIES FROM ABOUT 5 TO ABOUT 20 PERCENT BY WEIGHT OF A METAL SOAP SELECTED FROM THE GROUP CONSISTING OF MAGNESIUM STEARATE, CALCIUM STEARATE, ZINC STEARATE AND ALUMINUM STEARATE, FROM ABOUT 0.1 TO ABOUT 2 PERCENT BY WEIGHT OF A MICROCRYSTALLINE WAX HAVING A MELTING POINT IN THE RANGE OF FROM ABOUT 170*F. TO ABOUT 195*F., FROM ABOUT 68 TO 97 PERCENT BY WEIGHT OF WHITE MINERAL OIL HAVING A VISCOSITY IN THE RANGE FROM ABOUT 55 TO ABOUT 90 SAYBOLT SECONDS UNIVERSAL AT 100*F. AND FROM ABOUT 1 TO ABOUT 10 PERCENT OF A DISPERSING AGENT SELECTED FROM THE GROUP CONISITING OF FATTY ACID ESTERS OF GLYCOLS, GLYCEROL AND SORBITOL AND POLYOXYETHYLENE SUBSTITUTED FATTY ACID ESTERS OF POLYHYDRID ALCOHOLS. 